What is the treatment for cardiac amyloidosis?

Treatment of Cardiac Amyloidosis

The treatment of cardiac amyloidosis requires identifying the specific amyloid type first (AL vs. ATTR), followed by targeted therapy with daratumumab-based regimens for AL amyloidosis and tafamidis for ATTR amyloidosis to reduce mortality and improve quality of life. 1

Diagnosis and Classification

Before initiating treatment, accurate diagnosis and typing of amyloidosis is essential:

1. Tissue diagnosis:

   • Definitive diagnosis requires tissue biopsy showing Congo red staining with apple-green birefringence under polarized microscopy 1
   • Common biopsy sites: abdominal fat pad, gingiva, rectum, bone marrow, or affected organs 1

2. Amyloid typing:

   • AL amyloidosis: Requires serum free light chain (sFLC) assay, serum/urine immunofixation electrophoresis, and bone marrow biopsy 1
   • ATTR amyloidosis: Bone scintigraphy (Tc-PYP scan) with exclusion of monoclonal protein 1, 2
   • Genetic testing for hereditary (ATTRv) vs. wild-type (ATTRwt) 2

Treatment by Amyloid Type

AL Amyloidosis Treatment

1. First-line therapy:

   • Daratumumab with bortezomib, cyclophosphamide, and dexamethasone (Dara-CyBorD) is the preferred regimen 1
   • Goal: Eradicate pathological plasma cells and remove affected light chains from circulation 1

2. For eligible patients:

   • Consider high-dose melphalan followed by autologous stem cell transplantation (HDM/SCT) 1, 3
   • Eligibility is based on risk assessment, with cardiac involvement being a major determinant 1

3. Monitoring:

   • Regular assessment of hematologic response 1
   • Careful monitoring for cardiac decompensation during therapy 1

ATTR Amyloidosis Treatment

1. First-line therapy:

   • Tafamidis (VYNDAQEL 80 mg or VYNDAMAX 61 mg once daily) for patients with NYHA class I-III symptoms 2, 4
   • Reduces cardiovascular mortality and hospitalizations 2, 4

2. Alternative options (if tafamidis is unavailable/not tolerated):

   • Diflunisal (with monitoring of renal function) 2
   • EGCG (green tea extract) 2

3. Advanced options:

   • For hereditary ATTR: Consider liver transplantation or combined heart-liver transplantation 2, 3

Supportive Heart Failure Management

1. Volume management:

   • Diuretics are the mainstay of therapy but use cautiously to avoid hypotension 1
   • Monitor for underfilling of stiff heart 1

2. Medications to use with caution or avoid:

   • Avoid digoxin (binds to amyloid fibrils causing toxicity even with normal levels) 1
   • Avoid calcium channel blockers (risk of exaggerated hypotension) 1
   • Use beta-blockers cautiously (cardiac output is heart rate dependent in restrictive physiology) 1
   • Use ACE inhibitors/ARBs cautiously due to hypotension risk 1

3. Anticoagulation:

   • Anticoagulate all patients with atrial fibrillation regardless of CHA₂DS₂-VASc score 2
   • Consider anticoagulation even in sinus rhythm if atrial mechanical dysfunction is present 1

Multidisciplinary Approach

1. Team collaboration:

   • Cardiology: Monitor cardiac function and manage heart failure 1
   • Hematology: Direct plasma cell-targeted therapy for AL amyloidosis 1, 3
   • Neurology: Assess and manage neuropathy 3
   • Nephrology: Manage renal involvement 3
   • Palliative care: Address symptoms and quality of life 1

2. Regular monitoring:

   • Cardiac biomarkers (BNP/NT-proBNP, troponin) 1
   • Echocardiography to assess response 5
   • Serum free light chains for AL amyloidosis 1

Common Pitfalls and Caveats

1. Diagnostic delays are common and detrimental to outcomes 6

   • Don't rely solely on SPEP/UPEP to exclude AL amyloidosis (lower sensitivity) 1
   • Consider amyloidosis in patients with unexplained heart failure with preserved ejection fraction

2. Treatment toxicity:

   • AL amyloidosis patients are at higher risk for treatment-related toxicity 1
   • Monitor for cardiotoxicity of chemotherapeutic agents 1

3. Advanced disease:

   • Heart transplantation may be considered for end-stage disease, particularly in younger patients 1, 7
   • For AL amyloidosis, heart transplantation should be followed by HDM/SCT to prevent recurrence 7

By following this approach, early diagnosis and appropriate treatment can significantly improve outcomes in this previously devastating disease.